Hydrochloric Acid → 9-Benzyloxy-3-hydroxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)-nonanoic Acid Tert-Butyl Ester

HRID 131617Notes

Reaction equation

HRID 131617 reaction equation
Cl.[C:2]([O:6][C:7](=[O:39])[CH2:8][C:9](=[O:38])[C:10]([CH3:37])([CH3:36])[C:11](=[O:35])[CH:12]([CH3:34])[CH:13]([O:25][C:26]([O:28][CH2:29][C:30]([Cl:33])([Cl:32])[Cl:31])=[O:27])[CH:14]([CH3:24])[CH2:15][O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([CH3:5])([CH3:4])[CH3:3]>CO>[C:2]([O:6][C:7](=[O:39])[CH2:8][CH:9]([OH:38])[C:10]([CH3:37])([CH3:36])[C:11](=[O:35])[CH:12]([CH3:34])[CH:13]([O:25][C:26]([O:28][CH2:29][C:30]([Cl:32])([Cl:31])[Cl:33])=[O:27])[CH:14]([CH3:24])[CH2:15][O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([CH3:3])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 208175869-Benzyloxy-4,4,6,8-tetramethyl-3,5-dioxo-7-(2,2,2-trichloroethoxycarbonyloxy)-nonanoic Acid Tert-Butyl Ester

Product 1

HCID 208175859-Benzyloxy-3-hydroxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)-nonanoic Acid Tert-Butyl EsterYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A bomb liner was charged with (R)-RuBINAP catalyst (16.8 mg, 10.0 μmol). HCl (555 μL, 0.2N in MeOH) was added and the mixture was then sonicated for 15 sec. Then a solution of 69 (59.4 mg, 0.1 mmol) in MeOH (555 μL) was added and the mixture transferred to a Parr apparatus. The vessel was purged with H2 for 5 min and then pressurized to 1200 psi. After 17 h, the reaction was returned to atmospheric pressure and poured into a sat NaHCO3 aq solution. The aqueous layer was extracted three times with EtOAc. The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography (gradient hexane to hexane/EtOAc 88:12) to give 70 (dr>20:1 as judged by 1H NMR analysis) (47.6 mg, 80%) as a clear oil: 1H NMR (400 MHz, CDCl3) δ 1.06 (d, J=6.9 Hz, 3H), 1.11 (d, J=6.8 Hz, 3H), 1.14 (s, 3H), 1.18 (s, 3H), 1.47 (s, 9H), 2.05-2.12 (m, 1H), 2.35-2.40 (m, 1H), 3.31-3.37 (m, 2H), 3.51-3.54 (m, 2H), 4.11-4.14 (m, 1H), 4.46 (s, 2H), 4.72 (d, J=11.9 Hz, 1H), 4.80 (d, J=11.9 Hz, 1H), 5.05 (dd, J=5.0 and 6.7 Hz, 1H), 7.27-7.35 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 12.0, 15.0, 19.3, 21.7, 28.0, 35.6, 37.5, 41.7, 51.8, 71.3, 73.0, 73.3, 80.6, 81.3, 94.7, 127.5, 127.7, 128.3, 138.2, 154.1, 172.4, 216; IR (film, NaCl, cm−1) 3849, 2974, 2879, 1758, 1701, 1454, 1368, 1248, 1152, 926, 734; LRMS (ESI) calcd for C27H39O8Cl3Na [M+Na+] 619.1, found 619.2; [α]23D=−13.0 (c=0.4, CHCl3).

Workup

  1. customthe mixture was then sonicated for 15 sec
  2. customThe vessel was purged with H2 for 5 min
  3. additionpoured into a sat NaHCO3 aq solution
  4. extractionThe aqueous layer was extracted three times with EtOAc
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by flash chromatography (gradient hexane to hexane/EtOAc 88:12)

Sources & evidence

ORD record
ord-1861bb3a4577421da03b93bb34b337f6
Source dataset
uspto-grants-2008_06
Patent number
US07384964B2

Reaction notes

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